1. Field of the Invention
This invention relates to the use of trimazosin or a pharmaceutically acceptable acid addition salt thereof for retarding the development of arterial disease in mammals. More specifically it relates to a method for suppressing fibrosis of atherosclerotic plaques in mammals having atherosclerosis by administering to said mammals trimazosin or a pharmaceutically acceptable acid addition salt thereof.
2. Description of the Prior Art
Atherosclerosis, a disease of the arteries, is recognized to be the leading cause of death in the United States and Western Europe. The pathological sequence leading to atherosclerosis and occlusive heart disease has been described in detail by Ross and Glomset in New England Journal of Medicine 295, 369-377 (1976). The earliest stage in this sequence is the formation of "fatty streaks" (plaques) in the carotid, coronary and cerebral arteries and in the aorta. These in turn give rise to development of the "fibrous plaque", which consists of accumulated intimal smooth muscle cells laden with lipid and surrounded by extracellular lipid, collagen, elastin, and proteoglycans. The cells plus matrix form a fibrous cap that covers a deeper deposit of cell debris and more extracellular lipid. The lipid is primarily free and esterified cholesterol. The fibrous plaque forms slowly, and is likely in time to become calcified and necrotic, advancing to the "complicated lesion" which accounts for the arterial occlusion and tendency toward mural thrombosis and arterial muscular spasm that characterize advanced atherosclerosis.
Statistical evidence suggests that hyperlipidemia, and hypertension are primary risk factors in causing atherosclerosis. Treatment of atherosclerosis is, therefore, approached by attempts to control hypertension and hyperlipidemia, by dietary or pharmacological means. Some success has been achieved in reducing the incidence and severity of atherosclerosis by strict adherence to a prudent diet, by lowering plasma lipids with drugs or with ileal bypass surgery, and by lowering systemic blood pressure with diet or drugs. However, coronary heart disease remains a threat, even to individuals striving to control their risk factor levels. It has been speculated that every individual in the United States has some degree of atherosclerosis. This fact, along with the high associated mortality and the inadequacy of present treatment methods, establishes the need for an anti-atherosclerotic agent.
The use of trimazosin and its pharmaceutically acceptable acid addition salts as antihypertensive agents is described in U.S. Pat. No. 3,669,968; and their use for the treatment of congestive heart failure and ischemic heart disease is disclosed in U.S. Pat. No. 4,130,647.
However, in spite of the above-mentioned uses for trimazosin and its salts, there was, prior to the time of the present invention, no report of the intent to use trimazosin or its salts for retarding the development of atherosclerosis, and no appreciation of its role, or that of its pharmaceutically acceptable acid addition salts, in achieving said desirable goal.